A considerable amount of evidence indicates that glycosaminoglycans have a role in regulating aqueous outflow resistance. Recently, for the first time, this laboratory biochemically identified the glycosaminoglycans in the trabecular meshwork and also determined that a specific type of glycosaminoglycan, hyaluronic acid, has a significant influence on aqueous flow through the normal rabbit aqueous outflow pathway. In order to determine whether glycosaminoglycan distribution--hyaluronic acid, keratan sulfate, heparan sulfate, and hybrid dermatan sulfate-chondroitin sulfate--and their concentration in the trabecular meshwork are related in intraocular pressure, this application is focused on the effects of steroids on the individual types of glycosaminoglycans and on the modulation of intraocular pressure. Preliminary studies indicate that different types of steroids applied topically to rabbit eyes cause varying effects on intraocular pressure and that some of the steroids act competitively. Dexamethasone elevates intraocular pressure, whereas dexamethasone plus testosterone has no effect. This laboratory has used standard biochemical assays, on a microscale basis, to isolate and characterize the trabecular meshwork glycosaminoglycan profile. Preliminary studies indicate that the rate of synthesis of the individual types of glycosaminoglycans can be determined by the in vivo injection of glycosaminoglycan precursors--3H glucosamine and 35SO4--into the anterior chamber. The isolated labelled glycosaminoglycans (synthetic analysis) and unlabeleled glycosaminoglycans (bulk analysis) from the same experimental groups are characterized by cellulose acetate electrophoresis and identified by degradation with specific glycosaminoglycan enzymes and by gel filtration chromatography. These studies will further the understanding of a model of dexamethasone-induced ocular hypertension in rabbits, in which keratan sulfate decreased and the other types of glycosaminoglycans increased with dexamethasone treatment. The effects of the steroid preparations on the concentration and synthesis of the individual types of glycosaminoglycans in the trabecular meshwork will be evaluated and these results related to the effects of the steroids on intraocular pressure. The proposed animal studies may relate to the pathogenesis of a common, debilitating and often blinding disease, open-angle glaucoma.